The National Resource for Accelerator Mass Spectrometry (AMS) was established in 1999 to enable biomedical researchers to accurately quantify very low levels of radioisotopes while exploring fundamental issues in biology. In this renewal, we will expand our present capabilities by developing methods to study biochemical pathways and cellular processes at the level of the single cell and small groups of cells, which will allow our collaborators to study the effect of aging in yeast. The Resource will also develop methods to quantify endogenous processes, such as protein and DNA oxidation in higher organisms. This will facilitate the study of inflammatory diseases ranging from atherosclerosis to neurodegenerative disorders to cancer. To further these goals, we will develop a sample presentation technology that will enable the analysis of much smaller samples than can be currently processed, as well as techniques for speciation of biomolecules in such samples. Throughout the tenure of the grant we will continue to provide a resource to the research community that will include service to investigators familiar with AMS, training of investigators in the technology and dissemination of the Resource. Towards these goals, our specific aims are to: 1.) Develop protocols for the online combustion of eluents from separatory instruments and couple the products to a gas accepting ion source to increase the sensitivity of AMS. 2.) Increase the value and information content of AMS measurements by quantitating isotope content in isolates of uniformly isotope-labeled systems or by quantitating derivatized biomarkers of modification or function on specific macromolecules. 3.) Provide quantitation of effector and effect in biological systems using multiple isotopic tracers within sampled materials. We will achieve this by developing a robust and higher throughput process for 3H sample preparation and by leveraging against other funded isotope measurements at the Center for Accelerator Mass Spectrometry (CAMS). 4.) Provide high throughput and precise quantitation for collaborative and service users.